Genetic Variant SLC26A7:p.Ser138Phe (chr8-91295639-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_052832.4(SLC26A7):c.413C>T(p.Ser138Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC26A7
NM_052832.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

Publications

2 publications found

Variant links:

Genes affected

SLC26A7 (HGNC:14467): (solute carrier family 26 member 7) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. This gene has abundant and specific expression in the kidney. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Aug 2013]

SLC26A7 Gene-Disease associations (from GenCC):

congenital hypothyroidism
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics

SLC26A7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.756

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A7	NM_052832.4 link	c.413C>T	p.Ser138Phe	missense_variant	Exon 4 of 19	ENST00000276609.8	NP_439897.1	Q8TE54-1
SLC26A7	NM_134266.2 link	c.413C>T	p.Ser138Phe	missense_variant	Exon 4 of 19		NP_599028.1	Q8TE54-2
SLC26A7	NM_001282356.2 link	c.413C>T	p.Ser138Phe	missense_variant	Exon 5 of 20		NP_001269285.1	Q8TE54-1
SLC26A7	NM_001282357.2 link	c.-408C>T		5_prime_UTR_variant	Exon 5 of 19		NP_001269286.1	Q8TE54A0A087WZI7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8 link	c.413C>T	p.Ser138Phe	missense_variant	Exon 4 of 19	1	NM_052832.4	ENSP00000276609.3		Q8TE54-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251408

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111950

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.413C>T (p.S138F) alteration is located in exon 4 (coding exon 3) of the SLC26A7 gene. This alteration results from a C to T substitution at nucleotide position 413, causing the serine (S) at amino acid position 138 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.12

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

.;D;D;D;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.89

D;.;D;.;D

M_CAP

Uncertain

0.21

MetaRNN

Pathogenic

0.76

D;D;D;D;D

MetaSVM

Pathogenic

0.92

MutationAssessor

Uncertain

2.2

.;M;M;M;M

PhyloP100

5.2

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.9

D;D;.;D;D

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0060

D;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D;D

Vest4

0.72, 0.71, 0.72

MutPred

0.50

Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);Loss of relative solvent accessibility (P = 0.0071);

MVP

0.91

MPC

0.55

ClinPred

0.96

GERP RS

5.5

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.28

gMVP

0.57

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over